Several aliphatic ketones to which humans are exposed are known to potentiate the toxicities produced by various xenobiotics including chloroform and carbon tetrachloride. We investigated the possibility that the potentiation may be due to increases in the amount of specific forms of cytochrome P-450 that metabolize the toxicants. In support of this view treatment of animals with methyl butyl ketone (MBK) increased the total amount of cytochrome P-450 in the liver and induced a form of cytochrome P-450 that was similar in molecular weight to that induced by phenobarbital (PB). DE-52 anion exchange chromatography further indicated the similarity in the forms of cytochrome P-450 induced by MBK and PB. Moreover, microsomes from rats treated with MBK or PB metabolized CHC13 to COC12 more rapidly than did microsomes from untreated rats. Pretreatment of rats with MBK also potentiated the hepatotoxicity and renal CHC13 by increasing the amounts of a form(s) of cytochrome P-450 that metabolizes CHC13 to the toxic metabolite COC12. Other ketones, such as acetone, may also change the composition of liver cytochrome P-450.